Immunolocalization of a Novel Collectin CL-K1 in Murine Tissues

Abstract

We have recently identified a novel collectin, CL-K1, that may play a role in innate immunity as a member of the collectin family. In this study using mice, we investigated the tissue distribution of CL-K1 for better understanding of its pathophysiological relevance. Real-time PCR analyses demonstrated that CL-K1 mRNA was expressed in all tissues tested. Immunohistochemical analyses demonstrated that CL-K1 was expressed in proximal tubules of kidney, in mucosa of the gastrointestinal tract, and in bronchial glands of bronchioles similar to the localization of SP-A and SP-D in these pulmonary structures. Immunohistochemistry also showed that CL-K1 was highly expressed in hepatocytes around the central veins in liver, which suggests that murine CL-K1 may be mainly produced in the liver and secreted into the blood stream as is human CL-K1. CL-K1 was especially detected in vascular smooth muscle in several types of tissues. In addition, it was also expressed in intestinal Paneth cells, in mesangial cells of kidney, in pancreatic islet D cells, and in neurons of the brain. It is of interest that this profile of CL-K1 expression is unique among the collectins. Together these histological findings may be useful for understanding the biological function of this novel collectin.

Collectin-11 detects stress-induced L-fucose pattern to trigger renal epithelial injury

“…Complement activation that proceeds through MASP-2 but does not subsequently require C4 has been reported in several organ models of stress-induced injury including postischemic injury of the heart, intestine, and kidney (26,27). Since CL-11 is expressed within these organs (3,4,11), it is possible that CL-11-mediated lectin pathway activation underpins a common trigger mechanism. In contrast to CL-11, we found no evidence to support a significant role of MBL in our model, since complement deposition on cells largely failed when CL-11 was absent, even though MBL was present (in serum) in our experiments.…”

“…The plasma concentration of CL-11 (12,13) is approximately one-tenth the concentration reported for MBL (2 μg/ml), albeit in a different study population (14). In addition, whereas MBL mainly originates by hepatocyte synthesis (15), CL-11 is synthesized at multiple tissue sites including the liver, brain, and heart, as well as in those systems cited above (3,4,11).…”

“…The broad expression of CL-11 (3,4,11) and its putative ligands (3, 11) makes it possible that CL-11 operates on a wider scale, promoting inflammation and immunity in other organs and conditions. Furthermore, the simplicity with which soluble monosaccharide inhibstrate that it is the locally produced CL-11 in the kidney that triggers renal ischemic injury in a MASP-2-dependent fashion, since our transplantation experiments clearly show that the implantation of Colec11 -/-kidneys into CL-11-sufficient (and CL-10-sufficient) WT mice achieves a significant degree of protection against ischemia-reperfusion damage.…”

“…Collectin-11 (CL-11, also known as CL-K1 and encoded by COLEC11) is a recently described component of innate defense that is synthesized by several types of nonimmune cells, including epithelial cells of the renal tract and mucosal cells in the intestinal and bronchial tracts (3,4). The collectin family of innate immune molecules to which CL-11 has been assigned (5) are soluble C-type lectins involved in pattern recognition and include mannan-binding lectin (MBL) and the surfactant proteins SP-A and SP-D (6,7).…”

Heteromeric Complexes of Native Collectin Kidney 1 and Collectin Liver 1 Are Found in the Circulation with MASPs and Activate the Complement System

“…CL-K1 is expressed primarily by cells in the adrenal gland, kidney, and liver. Our previous studies using mainly recombinant CL-K1 indicated that it largely forms monomers and dimers of individual subunits, although larger oligomers were also detected in the circulation (6,12,16). Recently, it was shown that defects in human CL-K1 or MASP-3 are strongly associated with a defect related to midline development called 3MC syndrome (17,18), and these findings suggest a role for complement components in developmental processes.…”